There are two principle types of Vitamin D, Vitamin D2 and D3. Vitamin D2 (ergocalciferol) is derived from such sources as fortified milk, herring, mackerel, tuna, salmon, sardines, eggs, fortified cereals, and baked goods, while Vitamin D3 (cholecalciferol) is a pro-hormone and an essential nutrient produced in the skin with exposure to UV rays, consumption of animal products and fortified foods. Vitamin D3 can be produced photochemically by the action of sunlight or ultraviolet light from the precursor sterol 7-dehydrocholesterol, which is present in the epidermis or skin. Vitamin D3 can also be consumed in the form of fish oil or foods, such as eggs or fish. Analogs of Vitamin D may be produced synthetically.
Vitamin D2 and D3 are subsequently 25-hydroxylated in the liver to form 25-hydroxyvitamin D2 (25OHD2) and 25-hydroxyvitamin D3 (25OHD3), respectively. 25OHD2 and 25OHD3 represent the main body reservoir and transport form of vitamin D and are stored in adipose tissue or are tightly bound by a transport protein while in circulation.
The exact levels of 25OHD2 and 25OHD3 that reflect optimal body stores are uncertain. Mild to modest deficiency can be associated with osteoporosis or secondary hyperparathyroidism. Severe deficiency may lead to failure to mineralize newly formed osteoid in bone, resulting in rickets in children and osteomalacia in adults.
Deficiency of Vitamin D is generally due to inadequate exposure to the sun or due to its low content in the diet. As early as the 1980's, it was found that the ethnic Saudi population has low Vitamin D. Extensive studies have shown that deficiency exists not only in the winter, but also in the summer months due to non-exposure to the sun. It has been found in the healthy Saudi population that Vitamin D deficiency exists in about 40-60% of men and women over 50 years of age. Recent studies put the deficiency of Vitamin D at 95-100%.
For any drug, large proportions of oral prescriptions are never taken at all. Recent estimates for noncompliance range from study to study, with ranges of 62 to 84 percent using electronic monitoring. In other words, many do not comply with the recommended dosages of oral prescriptions.
Conventional routes of administration of Vitamin D include oral or injectable administration. For oral Vitamin D and calcium supplementation, the compliance is reported between 20-60%. It has been reported that at the end of 3 months, only 23.8% of patients were taking the supplementation and another 26.2% were partially compliant. Physicians attempted to address this problem by prescribing monthly, quarterly and yearly dosages. A yearly oral dose of 500,000 international units was found to result in an increased risk of falls and fractures. Recently, quarterly dosages of 150,000 IU of Vitamin D and intermittent large doses of vitamin D have been found to be ineffective.
Deficiency of Vitamin D is often significant in those who are non-compliant, i.e., fail to take prescribed dosages of oral Vitamin D. Typically, non-compliance is associated with patients who are already required to take a number of other oral medications. It was reported that between 40-45% of patients become non-compliant within six months of initiating therapy for osteopenia and osteoporosis. It was found that about 12% of elderly U.S. patients take ≧12 medications and 23% take at least 5 prescription medications. Requiring additional oral medications becomes burdensome for such patients. As Vitamin D is an essential part of osteopenia and osteoporosis treatment, a suitable alternative is desirable. An alternative to oral supplementation would likely increase compliance of patients already burdened with other oral medications.
Thus, a topical composition with vitamin D3 solving the aforementioned problems is desired.